The primary goals of the Solid Tumors Program are to develop novel molecularly-targeted approaches for prevention and treatment of malignancies arising from mucocutaneous, urogenital, and gut epithelia and mesenchymal tissues and to design and conduct translational clinical trials based on findings in basic and/or population research studies. There are 27 full and 9 associate members in this program. Members have 126 active funded projects, which provide over $22 million in funding. Of these, 27 NCI grants account for $3.3 million. Program 3 researchers apply cellular, molecular biological, and genetic techniques to advance understanding of molecular pathogenesis. This new program evolved by integrating two original programs, the well-established Hormonal and Reproductive Cancers and The Gastrointestinal Malignancies Programs. The newly organized program incorporates research work reviewed favorably in the previous competing renewal into a research network optimally supportive for translational research, an area of previous concern. Research in this new program involves studies of normal and malignant cells, as well as inherited diseases that predispose to the development of epithelial malignancies by combined mechanisms of genetic instability and microenvironmental perturbations. Translational studies along with Program 2, Hematologic, have led us to discover, develop, and deliver new treatments for solid tumors, highlighted by molecular therapy of GISTs. Our members have defined new standards of care for total colonic surveillance in colorectal cancer, determined the role of stem cell transplant in poor-risk germ cell cancer, and improved prostate cancer therapy using high-dose calcitriol. We also have developed new murine conditional-knockout models of epithelial carcinogenesis, discovered Herstatin (an inhibitor of EGF and Her2/neu signal transduction) and are clarifying an essential role of IGF signaling and Fanconi pathway dysfunction in clonal progression of epithelial malignancies of the prostate and ovary. The program provides a successful framework that promotes interactions between basic scientists involved in research on epithelial cell survival, differentiation, and clonal evolution and clinicians treating these disorders who also develop translational clinical trials.